p53 Inhibits Cell Growth as well as Cell Proliferation

Michael Karin, Ph.D.
University of California San Diego
NIEHS Grants R01ES006376, R37ES004151, and P42ES010337.

New research findings by NIEHS grantees at the University of California at San Diego that the tumor suppressor gene p53 is involved in regulating the growth of cells as well as the proliferation of cells. p53 target genes that inhibit cell proliferation had long been known, but its targets for inhibiting cellular growth were unknown.

Abnormal cell proliferation and growth of cells are characteristics of cancer. The p53 protein acts in the cell nucleus to control the expression of other genes whose products can inhibit cell proliferation and growth. The researchers discovered that two p53 target genes, known as Sestrin1 and Sestrin2, provide an important link between p53 and a protein kinase called mTOR, a central regulator of cell size. Incidentally, mTOR is the target for the immunosuppressive drug rapamycin, which was recently shown to have anti-cancer activity.

The major tumor suppressor p53 can either inhibit cell proliferation and cell growth or induce cell death. Its different functions are mediated through numberous target genes and depend on the extent of damage to the cell. More than half of all human cancers are either missing p53 expression or express a defective version of the protein. Understanding the mechanisms by which p53 suppresses tumors may lead to the development of new cancer preventives and chemotherapeutic agents.

Citation: Budanov AV, Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. 2008 Aug 8;134(3):451-60.